In the early 1990s, a number of major events took place in the history of the treatment and science of ALS. A cause of familial ALS, the mutation of superoxide dismutase 1, was discovered and very shortly after, an animal model expressing the human SOD1 mutation for familial ALS was generated. Around the same time, the first medication for the treatment of ALS, riluzole, was approved. Clinical neurologists started to focus more attention on quality of life and standardizing care for patients with ALS, including devising approaches for presenting and discussing the diagnosis, using aggressive symptomatic treatments, and developing a multidisciplinary care system. Since then, nutritional and respiratory care has markedly improved. Respiratory care for those with terminal ALS in Japan has been distinct and perhaps more effective compared to the rest of the world, and this unique experience must be broadly published and shared with others. In 1999, the ALS Treatment Guidelines were published by the American Academy of Neurology and are now under revision. A monitoring system to determine the impact the Guidelines had on actual patient care has taught us that caregivers have only slowly accepted the recommendation to improve quality of care. The team approach, using a multidisciplinary care system from diagnosis to the end of life, is essential to improve care for both the patient and family. Coinciding with the progress in ALS treatment, basic science and translational research also produced dramatic progress in ALS drug discovery. Over the past 15 years, more than 25 potential drugs have been tested in randomized controlled trials. Despite this progress, we have no medications other than riluzole. Although it may be true that ALS research is in its early stages compared to research in other diseases with no cure--it is probably behind cancer research by at least 20 or 30 years--we need to drastically change our approach to drug development. At a national level, we need to create a strong, cohesive team with support from a number of funding agencies, oversight from a regulatory agency, and investigators who all think "outside the box." In addition, we should obtain ideas and suggestions from accomplished experts outside of the field of ALS and put competition aside as we work together to develop strategic plans for the ALS drug development that is essential to beat this devastating disease.